Halogenated acenaphthoyl alkanoic acids



Patented June 20, 1950 UNITED PATENT OFFICE HALOGENATED-ACENAPHTHOYL ALKANOIC ACI Robert RfiBurtner; Skokie, 111., assignor .to Gt-D.

ESearlef&= Goua'jskokie, 111., a corporation of Illinois No Drawing. ApplicationApril"6,*1948, Serial No. 19,435

8 Claims. (Cl. 260515) :1 i This invention relates to' acenaphthoylalkanoic acids which are substituted-,-in the alkanoic acid radical by halogenation, to salts of these acids, and to processes 'forpreparing these acids and salts. Moreparticularly, it concernsketo" acids of the general structural formula:

wherein ;R is a trivalentaliphaticf hydrocarbon radical and X ishalogen.

In the foregoing structural formula,-'-R-represents a trivalent saturated aliphatic hydrocarbon radical containing 2 to 8 carbon-atoms. "It therefore represents halogen-substituted radicals such as ethylene; propylene, trimeth'ylene, 1,2-butylene, 2,3 -butylene, tetramethylene, amylene, and related polymethylene radicals including octamethylene, .as well as branched-chain alkylene radicalsof the same number of carbon atoms.

.Xstands for halogen atoms such as chlorine,

iodine, or bromine. The halogen substituent X is believed to'be in the a positiom'that is, adjacent to theketo grouping.

-The compounds of this invention are useful intermediates in the preparation of complex organic compounds such as steroids, dyestuffs,

and medicinal agents. The compoundsarefu'r- 'thermore of value as pharmaceuticals, plasticizers,and pesticides. It is the object of this invention to provide useful substances of the fore- ;going general type for the purposes recited above. It is a further object of this invention to provide efficient methods for obtaining such materials.

-My invention is disclosed in further detail by the following compounds, which arerepresentative of those within its scope:

A. I ,B--acenaphthoyl ,8 bromopropionic acid, which has the formula CHa-CH:

V2 p B. w-5-acenaphthoyl-w-bromopelargonic acid, having the formula C. 6-3-acenaphthoylec-bromovaleric acid, of the formula CHa-CH:

=1D.. 5 5 acenaphthoy1- a chlorovaleric -which hasthe formula C'HFCH:

acid,

yiof the formula G. -3-acenaphthoyl-'y-bromobutyric acid, of the formula H. --acenaphthoyl-'y-chlorobutyric acid, of the formula I. 5-3-acenaphthoyl-fi-bromopropionic acid, having the formula GHQ-CH2 ,my copending application Serial No. 6,339, filed February 4, 1948.

My invention is further disclosed by means of the following examples, which are set forth for the purpose of illustration and which in no way are to be construed as limiting my invention in spirit or in scope. It will be apparent to those skilled in the art that innumerable conventional modificati0ns in solvent, temperature, catalyst J. 'y5acenaphthoyl-v-bromoisovaleric acid, of

the formula C Hz-C Hz The compounds of my invention are obtained 4 by halogenating an acenaphthoylalkanoic acid, preferably in the presence of an inert solvent such as acetic acid, carbon tetrachloride, chloroform, related halogenated hydrocarbon solvents, hydrocarbons such as cyclohexane, saturated petroleum hydrocarbon fractions, benzene, and the. like. For halogenation agents, I prefer to use the free halogens, that is, elemental bromine or chlorine. Other halogenation agents, however, are suitable,

among them being sulfuryl chloride or bromide,

phosphorus tribromide or trichloride, and N-bromosuccinimide. One equivalent of halogenating agent is sufficient for the reaction and excesses are to be avoided. The halogenation reaction is preferably carried out under anhydrous conditions at slightly elevated temperatures, preferably between and 100 centigrade, although lower temperatures are often satisfactory. The halogenation reactions generally take place very rapidly, and are usually complete within a matter of a few minutes. In certain instances it may be necessary to carry the reaction out over longer periods of an hour or two. After the reaction is complete, the solvent is removed and the halogenated keto acid is obtained in a state of purity as a residue. This may be crystallized and purified by conventional procedures.

alkaline carbonate solution, such as sodium carbase. The salts are often insoluble in the alcohol and may be obtained as precipitates. In other and reagents can be adopted without departure from the intent and purpose of this invention. Quantities of materials are given in parts by weight unless otherwise noted.

Example 1 A suspension of 164 parts of finely powdered B-(5-acenaphthoyl)propionic acid in 1640 parts of glacial acetic acid is stirred vigorously at 60 C. while a solution of 102.4 parts of bromine in 330 parts of glacial acetic acid is added dropwise, the temperature being maintained at 57-63 C. The addition takes approximately 1 hour. At the end of this time, the mixture is heated to 65-70" C. for a few minutes in order to complete the reaction. The mixture is then chilled and stirred for 30 minutes. About half the acetic acid is removed under reduced pressure. The residue is chilled, and the precipitate of B-bromo- ,8-(5-acena hthoyl)propionic acid (compound A) is removed by filtration and dried. This acid, after recrystallization from acetic acid, melts at about 165 C. (with decomposition).

Example 2 A solution of 7'7 parts of acenaphthene and 57 parts'of methylsuccinic anhydride (pyrotartario anhydride) in 600 parts of nitrobenzene is chilled to 0 C, i33'parts of anhydrous aluminum chloride are added in small portions with vigorous agitation, while the temperature is maintained between 0 and 2 C. After the addition of aluminum chloride, the mixture is kept at room temperature for 40 hours. It is then decomposed with 500 parts of ice and parts of concentrated hydrochloric acid. The nitrobenzene is removed by steam distillation, and the brown, granular residue thus obtained is dissolved in a hot solution of vand the crude precipitate of ,B-(B-acenaphthoyDisObutyric acid is formed. This is converted into its methyl ester by refiuxingfor 5 hours with 400 parts of methanol containing 46 parts of concentrated sulfuric acid. The hot methanolic solution is treated with decolorizing charcoal and filtered. Upon chilling, a small amount of tarry material forms, which is discarded. On continued chilling a crystalline precipitate forms. This is removed and recrystallized from petroleum ether with the use of decolorizing charcoal, to form white crystals of ,8-(5-acenaphthoyDisobutyric acid methyl ester melting at 93-94 C.

ing 62 parts of sodium carbonate.

ncreases 'The' purified-ester issaponified by rfluxin'g with 250 parts of 10 imethanolicpotassium hydroxide for 1 l hour. The" chilled solution is poured into a mixture of 240 partsof'concentrated hy drochloric acid and 500 parts of icew-ater. The precipitate of fl-(5-acenaphthoyl)isobutyric acid is recrystallized from 75% methanol/andthen from benzene, and forms white crystals melting at 177-l79 C. Bromination of 2'7 parts of this acid by the procedure of Example lgvusing 16 parts of bromine and-'1000 parts orrhoti glacial acetic acid at 75-80 0., affords B-(5-acenaphthoyl) -;8-bromoisobutyric acid (compound E). This is isolated by removal of "solvent un-der'vacuum, addition-of ice water, decantatio-n, granulation and filtration.

Example 3 A solution of 631 partscf acenaphthene and 475 parts of glutaricanhydridein'5000 parts of nitrobenzene is2cooledttoc0z0 Then 1-0901parts of anhydrous aluminum chlorideareadde'd-portionwise with :stirring, the temperature being maintained at -3 C. After the aluminum chloride is added, the mixture is stirred for tWo'hours at iceWemperature-andthen-allowed to stand overnight, coming to room temperature during the period. The reaction mixture is quenche-dby pouring onto.10,000, parts zof'ice containing 1800 parts .ormuriatic acid. The nitrobenzene is .re-

moved by steam distillation and the residue is chilled. The granular precipitateis removed by filtration, ground to a thin suspension in water, collected on a filter and washed with water. This is taken up in 6700 parts of boiling water containing 340 parts of sodium carbonate. solution is filtered to remove acenaphthene, and the filtrate is chilled and acidified. The crude --acenaphthoylbutyric acid is collected on a filter, washed, and dried, It is recrystallized from acetic acid using decolorizing charcoal, and forms sand-colored crystals melting at l67-169 C. Further recrystallization from acetic acid and from butyl acetate raises the melting point to PIS-180 C.

36 parts of -fi-acenaphthoylbutyric acid in 220 parts of methanol containing 26 parts of sulfuric acid are refluxed for 11 hours. The solution is then poured into 1200 parts of Water contain- The mixture is stirred for minutes and filtered. The filter cake of methyl y-5-acenaphthoylbutyrate is Washed with water and dried. After recrystallization from ethanol this ester melts at 121 C. parts of this ester are refluxed for 40 minutes in 240 parts of ethanol containing 15 parts of caustic potash. The crystalline potassium salt is removed from the chilled solution and dissolved in water. Upon acidification, 'y-5-acenaphthoylbutyric acid is obtained, melting at about 203 C. Recrystallization from acetic acid does not change this melting point.

All the mother liquors obtained from the recrystallization of 'y-d-acenaphthoylbutyric acid are combined and stripped of solvent under vacuum. The crude -3-acenaphthoylbutyric acid thus obtained is esterified by refluxing for 10 hours in a solution of 2200 parts of methanol containing 250 parts of concentrated sulfuric acid. The solvent is removed and the residue is poured into dilute sodium carbonate solution. The methyl 'y-3-acenaphthoylbutyrate is extracted With ether, washed with water, dried and evaporated. It is crystallized from petroleum ether, and melts at 68 C. 295 parts of the crystalline ester are refluxed for minutes in 2400 parts of The hot I:

ethanol containm'g. 200 xarts :of rcaustic :potas'h. I The solve'ntl is then stripped zoffzin vacuumand the residue of tpota'ssium' ye3 a cenaphthoylbutyrate is taken up iin 24000 xparts :sof i water. -..U.pon acidification -3-acenaphthoylbutyricacid lmeltingaataboutififr 1C.i is :isoiated. Recrystallization from ethanol does not raiseithisicmeltingcpoint.

134 parts of 'y-3-acenaphthoy lbutyric acid in 5000 parts of hot acetic acid are reacted with parts of bromine in 200 parts of'aceticacid over a periodof .20minutes. The temperature is kept at '75-85 C. during the reaction. AfterEan hour the solvent is removed and the residue is poured -intm-about 2-500 parts of ice -water. Theproduct so obtained ::is w-(3eacenaphthoyliw-bromobu- Jtyr-icacid compoundfi) *Erample el .--14.1 :parts .of 6-3-acenaphthoylva1eric acid (Burtner and Brown applicatiorrserial.No;- 6,804, filed February 6, 1948) dissolved in 5000 parts of hot acetic acid are reacted at about 50 C., with agitation over a period of"5-.10 minutes, with 80 parts of bromine in 200 parts of acetic acid. The mixture is stirred for 30 minutes longer while it is allowed to cool to room temperature. Most of the acetic acid is stripped off under reduced pressure, and the residue'is diluted with 2000 parts of cold Water. The precipitate of 5-3- acenaphthoyl-tebromovaleric acid (compound C) .is removed bydecantation, washed with-methanol,

and-dried.

.Erample c5 A solution of 384 parts of bromine in 1100 parts of glacial acetic acid i added over a period of 20 minutes to a stirred suspension of 630 parts of ,8-B-acenaphthoylpropionic acid in 6300 parts of glacial acetic acid maintained at 58-62 C. The agitation is continued for 25 minutes after the addition is complete and then the solvent is removed by evaporation under reduced pressure. The residue of ,B-bromo-fi-(3-acenaphthoyl)propionic acid rapidly crystallizes. It is suspended in about 800 parts of cold benzene, filtered and then washed with cold benzene. Upon recrystallization from toluene in the presence of decolorizing charcoal B-bromo-fi-(ii-acenaphthoyDpropionic acid (compound I) forms yellow crystals melting at 167 C. (with decomposition).

I claim:

1. A member of the group consisting of an .acenaphthoyl-halo-alkanoic acid wherein the alkanoic acid radical contains three to nine carbon atoms and is attached to one of the positions of the acenaphthene nucleus numbered 3 and 5 and wherein the halo substituent is a halogen atom of atomic number greater than 9, and alkali metal salts thereof.

2. An acenaphthoyl-halo-alkanoic acid of the structural formula wherein X is halogen of atomic number greater than 9 and n is an integer not greater than seven and wherein the halogenated keto alkanoic acid radical is attached to one of the positions of the acenaphthene nucleus numbered 3 and 5.

4. An acenaphthoyl-halo-alkanoic acid of the structural formula wherein R is a trivalent aliphatic hydrocarbon radical containing two to eight carbon atoms and X is halogen of atomic number greater than 9.

5. An w-(5-acenaphthoyl) -w-haloalkanoic acid of the structural formula OHr-OH:

wherein X is halogen of atomic number greater than 9 and n is an integer not greater than seven.

6. An w-(5-acenaphthoy1) w bromoalkanoic acid of the structural formula wherein n is an integer not greater than seven.

'7. A 3-acenaphthoyl-,3-haloalkanoic acid. 8. fi-(5-acenaphthoyl) -18-bromopropionic acid.

ROBERT R. BURTNER.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,759,111 Greune May 20, 1930 1,889,347 Bruson Nov. 29, 1932 2,423,709 Knott July 8, 1947 OTHER REFERENCES Fieser et al.: J. Am. Chem. Soc, vol. 54, pp. 4347-4356 (1932). 

1. A MEMBER OF THE GROUP CONSISTING OF AN ACENAPHTHOYL-HALO-ALKANOIC ACID WHEREIN THE ALKANOIC ACID RADICAL CONTAINS THREE THE NINE CARBON ATOMS AND IS ATTACHED TO ONE OF THE POSITIONS OF THE ACENAPHTHENE NUCLEUS NUMBERED 3 AND 5 AND WHEREIN THE HALO SUBSTITUENT IS A HALOGEN ATOM OF ATOMIC NUMBER GREATER THAN 9, AND ALKALI METAL SALTS THEREOF. 